ArticleThe Journal of allergy and clinical immunology2015
CTNNA3 and SEMA3D: Promising loci for asthma exacerbation identified through multiple genome-wide association studies.
Article in The Journal of allergy and clinical immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- A genome-wide association study of severe asthma exacerbations in Latino children and adolescents.The European respiratory journal · 2021Pooled it
- Systems biology and in vitro validation identifies family with sequence similarity 129 member A (FAM129A) as an asthma steroid response modulator.The Journal of allergy and clinical immunology · 2018Trial
- Chromosome 21 variants tied to severe asthma exacerbations: A genome-wide association study in a Brazilian population.The journal of allergy and clinical immunology. Global · 2025Article
- Genomic Regions Associated with Respiratory Disease in Holstein Calves in the Southern United States.Genes · 2025Article
- Identification of novel loci associated with starch content in maize kernels by a genome-wide association study using an enlarged SNP panel.Molecular breeding : new strategies in plant improvement · 2023Article
- Leveraging genetic ancestry to study severe asthma exacerbations in an admixed population.Thorax · 2023Article
- Bioinformatics and Next-Generation Data Analysis for Identification of Genes and Molecular Pathways Involved in Subjects with Diabetes and Obesity.Medicina (Kaunas, Lithuania) · 2023Article
- Asthma Exacerbations: Patient Features and Potential Long-Term Implications.Advances in experimental medicine and biology · 2023Article
- Alpha-T-catenin is expressed in peripheral nerves as a constituent of Schwann cell adherens junctions.Biology open · 2022Article
- SEMA3D Plays a Critical Role in Peptic Ulcer Disease-Related Carcinogenesis Induced byInternational journal of general medicine · 2022Article
- The Predictive Role of Biomarkers and Genetics in Childhood Asthma Exacerbations.International journal of molecular sciences · 2021Review
- Genome-wide association study reveals a novel locus for asthma with severe exacerbations in diverse populations.Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · 2021Article
- Free Feeding of CpG-Oligodeoxynucleotide Particles Prophylactically Attenuates Allergic Airway Inflammation and Hyperresponsiveness in Mice.Frontiers in immunology · 2021Article
- Exacerbation-Prone Asthma.The journal of allergy and clinical immunology. In practice · 2020Article
- Elucidation of causal direction between asthma and obesity: a bi-directional Mendelian randomization study.International journal of epidemiology · 2019Article
- Large-scale, multiethnic genome-wide association study identifies novel loci contributing to asthma susceptibility in adults.The Journal of allergy and clinical immunology · 2019Article
- Lessons Learned From GWAS of Asthma.Allergy, asthma & immunology research · 2019Review
- Article
- Epigenomics and Transcriptomics in the Prediction and Diagnosis of Childhood Asthma: Are We There Yet?Frontiers in pediatrics · 2019Review
- Genetic variants with gene regulatory effects are associated with diisocyanate-induced asthma.The Journal of allergy and clinical immunology · 2018Article
Corrections and comments
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Authors and funding
18 authors at 7 institutions in 2 countries.
Funding
Abstract
backgroundAsthma exacerbations are a major cause of morbidity and medical cost.
objectiveThe objective of this study was to identify genetic predictors of exacerbations in asthmatic subjects.
methodsWe performed a genome-wide association study meta-analysis of acute asthma exacerbation in 2 pediatric clinical trials: the Childhood Asthma Management Program (n = 581) and the Childhood Asthma Research and Education (n = 205) network. Acute asthma exacerbations were defined as treatment with a 5-day course of oral steroids. We obtained a replication cohort from Biobank of Vanderbilt University Medical Center (BioVU; n = 786), the Vanderbilt University electronic medical record-linked DNA biobank. We used CD4(+) lymphocyte genome-wide mRNA expression profiling to identify associations of top single nucleotide polymorphisms with mRNA abundance of nearby genes.
resultsA locus in catenin (cadherin-associated protein), alpha 3 (CTNNA3), reached genome-wide significance (rs7915695, P = 2.19 × 10(-8); mean exacerbations, 6.05 for minor alleles vs 3.71 for homozygous major alleles). Among the 4 top single nucleotide polymorphisms replicated in BioVU, rs993312 in Sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3D (SEMA3D) was significant (P = .0083) and displayed stronger association among African Americans (P = .0004 in BioVU [mean exacerbations, 3.91 vs 1.53]; P = .0089 in the Childhood Asthma Management Program [mean exacerbations, 6.0 vs 3.25]). CTNNA3 variants did not replicate in BioVU. A regulatory variant in the CTNNA3 locus was associated with CTNNA3 mRNA expression in CD4(+) cells from asthmatic patients (P = .00079). CTNNA3 appears to be active in the immune response, and SEMA3D has a plausible role in airway remodeling. We also provide a replication of a previous association of purinergic receptor P2X, ligand-gated ion channel, 7 (P2RX7), with asthma exacerbation.
conclusionsWe identified 2 loci associated with exacerbations through a genome-wide association study. CTNNA3 met genome-wide significance thresholds, and SEMA3D replicated in a clinical biobank database.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.